This invention relates to examination and imaging of biological tissue using visible or infra-red radiation.
Traditionally, potentially harmful ionizing radiation (for example, X-ray or xcex3-ray) has been used to image biological tissue. This radiation propagates in the tissue on straight, ballistic tracks, i.e., scattering of the radiation is negligible. Thus, imaging is based on evaluation of the absorption levels of different tissue types. For example, in roentgenography the X-ray film contains darker and lighter spots. In more complicated systems, such as computerized tomography (CT), a cross-sectional picture of human organs is created by transmitting X-ray radiation through a section of the human body at different angles and by electronically detecting the variation in X-ray transmission. The detected intensity information is digitally stored in a computer which reconstructs the X-ray absorption of the tissue at a multiplicity of points located in one cross-sectional plane.
Near infra-red radiation (NIR) has been used to study non-invasively the oxygen metabolism in tissue (for example, the brain, finger, or ear lobe). Using visible, NIR and infra-red (IR) radiation for medical imaging could bring several advantages. In the NIR or IR range the contrast factor between a tumor and a tissue is much larger than in the X-ray range. In addition, the visible to IR radiation is preferred over the X-ray radiation since it is non-ionizing; thus, it potentially causes fewer side effects. However, with lower energy radiation, such as visible or infra-red radiation, the radiation is strongly scattered and absorbed in biological tissue, and the migration path cannot be approximated by a straight line, making inapplicable certain aspects of cross-sectional imaging techniques.
Several different approaches to NIR imaging have been suggested in the past. One approach undertaken by Oda et al. in xe2x80x9cNon-Invasive Hemoglobin Oxygenation Monitor and Computerized Tomography of NIR Spectrometry,xe2x80x9d SPIE Vol. 1431, p. 284, 1991, utilizes NIR radiation in an analogous way to the use of X-ray radiation in an X-ray CT. In this device, the X-ray source is replaced by three laser diodes emitting light in the NIR range. The NIR-CT uses a set of photomultipliers to detect the light of the three laser diodes transmitted through the imaged tissue. The detected data are manipulated by a computer of the original X-ray CT scanner system in the same way as the detected X-ray data would be.
Different approaches were also suggested by S. R. Arriadge et al. in xe2x80x9cReconstruction Methods for Infra-red Absorption Imaging,xe2x80x9d SPIE Vol. 1431, p. 204, 1991; F. A. Grxc3xcnbaum et al. in xe2x80x9cDiffuse Tomography,xe2x80x9d SPIE Vol. 1431, p. 232, 1991; B. Chance et al., SPIE Vol. 1431 (1991), p. 84, p. 180, and p. 264; and others who recognized the scattering aspect of the non-ionizing radiation and its importance in imaging. None of those techniques have fully satisfied all needs in tissue examination.
In summary, there continues to be a need for an improved system which utilizes visible or IR radiation of wavelengths sensitive to endogenous or exogenous pigments to examine or image biological tissue.
The invention relates to systems and methods for spectroscopic examination of a subject positioned between input and detection ports of the spectroscopic system applied to the subject.
According to one aspect, the invention features a spectroscopic system for examination of tissue of a subject, including: at least one light source of electromagnetic radiation of a visible or infrared wavelength selected to be scattered and absorbed while migrating in the tissue; at least two input ports, optically coupled to the light source, constructed to introduce at selected input locations of the examined tissue the radiation of known intensities that define a null plane in the tissue; a detection port located at a selected detection location of the examined tissue relative to the null plane; a detector, optically coupled to the detection port, constructed to detect during operation the radiation that has migrated in the examined tissue; a detector circuit connected to and receiving detection signal from the detector; the detector circuit including a sample-and-hold circuit and a subtraction circuit, both connected to the detector circuit, constructed to subtract detection signals corresponding to radiation that has migrated from a first input port to the detection port and from a second input port to the detection port, respectively, to obtain processed data; and a processor, connected to and receiving the processed data from the subtraction circuit, adapted to evaluate the examined tissue.
According to another aspect, the invention features a spectroscopic system for examination of tissue of a subject, including: a source of electromagnetic radiation of a visible or infrared wavelength; an input port, optically coupled to the light source, constructed to introduce at a selected input location of the examined tissue the radiation; a detector optically coupled to at least two detection ports located at selected detection locations defining a null plane in the examined tissue, the detector constructed to detect radiation that has migrated in the examined tissue-to the detection ports; a detector circuit connected to and receiving detection signal from the detector, the detector circuit including a sample-and-hold circuit and a subtraction circuit; the detector circuit constructed to correlate emission of the radiation from the input port with detection of radiation scattered and absorbed while migrating in the tissue at the first detection port, the detected radiation being stored as a first detection signal; the detector circuit further constructed to correlate emission of the radiation from the input port with detection of radiation scattered and absorbed while migrating in the tissue at the second detection port, the detected radiation being stored as a second detection signal; the subtraction circuit constructed to subtract the detection signals; and a processor, connected to and receiving the processed data from the subtraction circuit, constructed to evaluate the examined tissue.
Embodiments of the invention may include one or more of the following additional features.
The spectroscopic system may include intensity control means constructed to regulate intensities of radiation emitted from the first and second input ports. The intensity control means may be constructed to regulate the intensities in a manner that sweeps the null plane over at least a portion of the volume of the examined tissue.
The spectroscopic system may preferably include positioning means constructed to displace the detection port to detection locations corresponding to the null plane or positioning means constructed to displace the input ports to selected locations.
The spectroscopic system may preferably include detector controller means constructed to changes the relative sensitivity of detection at the first and second detection port in order to sweep the null plane over at least a portion of the volume of the examined tissue.
Preferably, the subtraction circuit includes an analog to digital converter, connected to the sample-and-hold circuit, constructed to digitize the detection signal to produce digital detection signal, the subtraction circuit subtracting the digital detection signals corresponding to radiation that ha s migrated from a first input port to the detection port and from a second input port to the detection port, respectively, to obtain the processed data. The processor may preferably be further adapted to locate, in the tissue volume, a tissue region exhibiting different scattering or absorptive properties than the rest of the examined tissue volume.
The input or detection ports may be preferably arranged in a linear array. The input or detection ports may be preferably arranged a two dimensional array. The spectroscopic may preferably further include an image processor, connected to and receiving the processed data from the processor, constructed to store processed data corresponding to different combinations of input and detection ports and create image data; and a display, connected to the image processor, constructed to display the image data representing the examined tissue.
The wavelength may be preferably sensitive to an endogenous pigment of the examined tissue. The wavelength may be preferably sensitive to an exogenous pigment of the examined tissue.
In another general aspect, the invention features a scheme for spectroscopic examination of tissue including the steps of: providing at least one light source of electromagnetic radiation of a visible or infrared wavelength selected to be scattered and absorbed while migrating in the tissue, the source being optically connected to at least two input ports, and a detection port optically connected to a detector, the detector connected to a detector circuit; positioning a first input port and a second input port relative to selected input locations of a subject; selecting for each input port first and second radiation intensities to be introduced to the tissue, the selected radiation intensities defining a null plane in the tissue; positioning the detection port relative to a selected detection location of the examined tissue corresponding to the null plane, the input locations and detection location defining a volume of the examined tissue of the subject; introducing into the subject, at the first input port, radiation of the first intensity; detecting, at the detection port, the first radiation that has migrated in the examined tissue; storing, in the detector circuit, a first detector signal corresponding to the first detected radiation; introducing into the subject, at the second input port, radiation of the second intensity; detecting, at the detection port, the second radiation that has migrated in the examined tissue; storing, in the detector circuit, a second detector signal corresponding to the second detected radiation; subtracting the first detector signal from the second detector signal to obtain processed data; and examining the tissue volume using the processed data.
The spectroscopic method may further include the step of selecting the first and second radiation intensities is preferably performed in a manner that sweeps the null plane over at least a portion of the volume of the examined tissue and the step of positioning the detector to detection locations corresponding to the swept null plane.
In another general aspect, the invention features a scheme for spectroscopic examination of tissue including the steps of: providing a source of electromagnetic radiation of a visible or infrared wavelength selected to be scattered and absorbed while migrating in the tissue, the source being optically coupled to an input port, and providing at least two detection ports optically coupled to at least one detector, the detector connected to a detector circuit; positioning the input port relative to selected input locations of the tissue; positioning a first detection port and a first detection port relative to selected detection locations of the examined tissue, the locations defining a null plane in the tissue a volume of the examined tissue of the subject; introducing into the tissue, at the input port, radiation of a selected intensity and a selected wavelength; detecting, at the first detection port, radiation that has migrated in the examined tissue and storing, in the detector circuit, a first detector signal corresponding to the detected radiation; detecting, at the second detection port, radiation that has migrated in the examined tissue and storing, in the detector circuit, a second detector signal corresponding to the detected radiation; and subtracting the first detector signal from the second detector signal to obtain processed data corresponding to properties of the tissue volume.
The detecting steps may be performed in a manner that changes the relative sensitivity of detection at the first and second,detection port in order to sweep the null plane over at least a portion of the volume of the examined tissue and the method may further include, simultaneously with the sweeping, positioning the input port to input locations corresponding to the swept null plane.
Further embodiments of the invention may include one or more of the following features.
The first detector signal and the second detector signal are preferably stored and subtracted in an analog form by the detection circuit. The spectroscopic method preferably further includes, before the storing steps, converting the first and second detection signals to a digital form, the subtracting step being performed digitally on the first detector signal and the second detector signal in an digital circuit.
The steps of positioning the input ports and the detection port at the respective selected locations preferably include placing the ports on the surface of the examined tissue. The steps of positioning the input ports at the respective selected locations preferably include orienting the input ports relative to the input is locations thereby enabling introduction of the radiation at the input locations of the examined tissue. The step of orienting the input ports preferably include directing an optical element of the input ports to the input locations. The positioning steps are preferably performed in a manner that sweeps the null plane and the detector over at least a portion of the volume of the examined tissue.
The spectroscopic method may further include locating, in the tissue volume, a tissue region exhibiting different scattering or absorptive properties than the rest of the examined tissue volume. The method may preferably further include imaging the examined tissue including the tissue region of different scattering or absorptive properties. The method may preferably further include displaying an image of the examined tissue by utilizing to the processed data and relative locations of the input ports and the output ports.
The method may preferably further include a step of introducing an exogenous pigment into the tissue and selecting a wavelength being sensitive to the pigment. The exogenous pigment may be preferentially accumulated in a tissue region exhibiting different scattering or absorptive properties. The exogenous pigment may be fluorescing when irradiated by selected wavelength, and the detecting steps may detect preferentially radiation wavelength of the fluorescing pigment.
In general, according to another aspect of the invention, a spectroscopic system includes at least one light source adapted to introduce, at multiple input ports, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density and of a wavelength selected to be scattered and absorbed while migrating in the subject, the input ports being placed at selected locations on the subject to probe a selected quality of the subject; radiation pattern controller adapted to achieve selected a time relationship of the introduced patterns to form resulting radiation that possesses a substantial gradient in photon density as a result of the interaction of the introduced patterns emanating from the input ports, the radiation being scattered and absorbed in migration paths in the subject. The system also includes a detector adapted to detect over time, at a detection port placed at a selected location on the subject, the radiation that has migrated in the subject; processor adapted to process signals of the detected radiation in relation to the introduced radiation to create processed data indicative of the influence of the subject upon the gradient of photon density; and the processor (evaluation means) adapted to examine the subject by correlating the processed data with the locations of the input and output ports.
According to another aspect of the invention, a spectroscopic system includes at least one light source adapted to introduce, at multiple input ports, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density and of a wavelength selected to be scattered and absorbed while migrating in the subject, the input ports being placed at selected locations on the subject to probe a selected quality of the subject; radiation pattern controller adapted to achieve a selected time relationship of the introduced. patterns to form resulting radiation that possesses a substantial gradient in photon density as a result of the interaction of the introduced patterns emanating from the input ports, the radiation being scattered and absorbed in migration paths in the subject. The system also includes a detector adapted to detect over time, at a detection port placed at a selected location on the subject, the radiation that has migrated in the subject; displacement means adapted to move the detection port to various locations on a predetermined geometric pattern, the various locations being used to detect over time radiation that has migrated in the subject; processor adapted to process signals of the detected radiation in relation to the introduced radiation to create processed data indicative of the influence of the subject upon the gradient of photon density; and the processor (evaluation means) adapted to examine the subject by correlating the processed data with the locations of the input and output ports.
According to another aspect of the invention, a spectroscopic system includes at least one light source adapted to introduce, at multiple input ports, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density and of a wavelength selected to be scattered and absorbed while migrating in the subject, the input ports being placed at selected locations on the subject to probe a selected quality of the subject; radiation pattern controller adapted to achieve a selected time relationship of the introduced patterns to form resulting radiation that possesses a substantial gradient in photon density as a result of the interaction of the introduced patterns emanating from the input ports, the radiation being scattered and absorbed in migration paths in the subject. The system also includes at least one detector adapted to detect over time, at multiple detection ports placed at selected locations on the subject, the radiation that has migrated in the subject; processor adapted to process signals of the detected radiation in relation to the introduced radiation to create processed data indicative of the influence of the subject upon the gradient of photon density, and the processor (evaluation means) adapted to examine the subject by correlating the processed data with the locations of the input and output ports.
Preferred embodiments of this aspect of the invention include displacement means adapted to move at least one of the detection ports to another location on a predetermined geometric pattern, the other location being used to perform the examination of the subject.
Preferred embodiments of this aspect of the invention include rotation means adapted to rotate synchronously the optical input ports while introducing the resulting radiation along a predetermined geometric pattern, the input port rotation being used to perform the examination of a region of the subject.
According to another aspect of the invention, a spectroscopic system includes a light source adapted to introduce, at an input port, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density and of a wavelength selected to be scattered and absorbed while migrating in the subject, the input port being placed at a selected location on the subject to probe a selected quality of the subject; detectors adapted to detect over time, at multiple detection ports placed at selected locations on the subject, the radiation that has migrated in the subject; the time relationship of the detection over time, at the detection ports, being selected to observe a gradient in photon density formed as a result of the interaction of the introduced radiation with the subject. The system also includes processor adapted to process signals of the detected radiation in relation to the introduced radiation to create processed data indicative of the influence of the subject upon the gradient of photon density, and the processor (evaluation means) adapted to examine the subject by correlating the processed data with the locations of the input and output ports.
According to another aspect of the invention, a spectroscopic system includes a light source adapted to introduce, at an input port, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density and of a wavelength selected to be scattered and absorbed by a fluorescent constituent while migrating in the subject, the input port being placed at a selected location on the subject to locate the fluorescent constituent of the subject; detectors adapted to detect over time, at multiple detection ports placed at selected locations on the subject, fluorescent radiation that has migrated in the subject. The system also includes processor adapted to process signals of the detected radiation in relation to the introduced radiation to create processed data indicative of location of the fluorescent constituent of the subject, and the processor (evaluation means) adapted to examine the subject by correlating the processed data with the locations of the input and output ports.
In certain preferred embodiments, the spectroscopic system further includes an image processor, connected to and receiving the processed data from the processor, constructed to store processed data corresponding to different combinations of input and detection ports and create image data, the image data including data of the tissue region; and a display, connected to the image processor, constructed to display the image data representing the examined tissue including the tissue region.
A displacement mechanism is adapted to move synchronously the optical ports and the detection ports to another location on a predetermined geometric pattern; this other location is used to perform the examination of the subject.
The spectroscopic system also uses a wavelength sensitive to endogenous or exogenous pigments of the examined biological tissue.
The spectroscopic system also used to locate a fluorescent constituent of interest in the subject; the wavelength of the introduced radiation is selected to be absorbed in the fluorescent constituent, the detected radiation is emitted from the fluorescent constituent and processed to determine location of the fluorescent constituent.
The time-varying pattern of resulting radiation is formed by the intensity modulated radiation introduced from each of the input ports having selected phase relationship that produces in at least one direction a steep phase change and a sharp minimum in the intensity of the radiation.
The phase relationship of the introduced radiation patterns is 180 degrees.
The modulation frequency of the introduced radiation has a value that enables resolution of the phase shift that originates during migration of photons in the subject.
Other features and adVantages will become apparent from the following description and from the claims.